Nonviral, plasmid-based therapeutics are a new class of pharmaceutical agents that offer the potential to cure many diseases that are currently considered untreatable. While nonviral vectors have shown promise in clinical trials, their physical instability in liquid formulations represents a major barrier to the development of these agents as marketable products. While several different approaches have been used to improve the stability of liquid formulations, it is unclear whether aqueous suspensions can be rendered sufficiently stable to withstand the stresses associated with shipping and storage. Some studies have demonstrated the potential of frozen formulations to be stored for prolonged periods of time, however the potential for phase changes in frozen samples combined with the expense of maintaining the frozen state during shipping has stimulated an interest in developing dehydrated preparations. Although the stresses associated with dehydration are considerable, several studies have reported that sugars are capable of preserving the physical characteristics and transfection activity of nonviral vectors during acute lyophilization stress. This paper discusses the merits and drawbacks of the different approaches to preserving nonviral vectors, and identifies research areas in which more work is needed to develop stable formulations of plasmidbased therapeutics.